CN113993519B - 细胞周期蛋白依赖性激酶12(cdk12)的降解剂及其用途 - Google Patents

细胞周期蛋白依赖性激酶12(cdk12)的降解剂及其用途

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CN113993519B
CN113993519B CN202080044331.9A CN202080044331A CN113993519B CN 113993519 B CN113993519 B CN 113993519B CN 202080044331 A CN202080044331 A CN 202080044331A CN 113993519 B CN113993519 B CN 113993519B
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CN113993519A (zh
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车建为
纳撒尼尔·S·格雷
张庭湖
江百山
高洋
尼古拉斯·保罗·克维亚特科夫斯基
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Dana Farber Cancer Institute Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/555—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN202080044331.9A 2019-04-23 2020-04-23 细胞周期蛋白依赖性激酶12(cdk12)的降解剂及其用途 Active CN113993519B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962837331P 2019-04-23 2019-04-23
US62/837,331 2019-04-23
PCT/US2020/029483 WO2020219650A1 (en) 2019-04-23 2020-04-23 Degraders of cyclin-dependent kinase 12 (cdk12) and uses thereof

Publications (2)

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CN113993519A CN113993519A (zh) 2022-01-28
CN113993519B true CN113993519B (zh) 2025-11-11

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Country Status (7)

Country Link
US (1) US20220227734A1 (https=)
EP (1) EP3958861A4 (https=)
JP (1) JP2022529700A (https=)
CN (1) CN113993519B (https=)
AU (1) AU2020263390B2 (https=)
CA (1) CA3132387A1 (https=)
WO (1) WO2020219650A1 (https=)

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WO2018165520A1 (en) 2017-03-10 2018-09-13 Vps-3, Inc. Metalloenzyme inhibitor compounds
CA3141826A1 (en) 2019-05-31 2020-12-03 Ikena Oncology, Inc. Tead inhibitors and uses thereof
CA3142351A1 (en) 2019-05-31 2020-12-03 Ikena Oncology, Inc. Tead inhibitors and uses thereof
CA3142713A1 (en) 2019-06-03 2020-12-10 Regents Of The University Of Minnesota Compounds that degrade kinases and uses thereof
AU2020321955A1 (en) 2019-07-30 2022-03-17 Eikonizo Therapapeutics, Inc. HDAC6 inhibitors and uses thereof
WO2022120355A1 (en) * 2020-12-02 2022-06-09 Ikena Oncology, Inc. Tead degraders and uses thereof
KR20240020735A (ko) 2021-05-07 2024-02-15 카이메라 쎄라퓨틱스 인코포레이티드 Cdk2 분해제 및 그 용도
IL312013A (en) * 2021-10-14 2024-06-01 Cullgen Shanghai Inc Modified proteins and protein degraders
US12084453B2 (en) 2021-12-10 2024-09-10 Incyte Corporation Bicyclic amines as CDK12 inhibitors
WO2023143482A1 (zh) * 2022-01-29 2023-08-03 上海辉启生物医药科技有限公司 2-氨基嘧啶类化合物或其盐及其制备方法和用途
TW202345813A (zh) 2022-04-08 2023-12-01 美商艾科尼佐療法股份有限公司 㗁二唑ｈｄａｃ６抑制劑及其用途
WO2024183798A1 (en) * 2023-03-07 2024-09-12 Cullgen Inc. Compounds and methods of treating cancers
CN119950745B (zh) * 2025-01-14 2025-10-17 浙江大学 一种药物组合物及其在制备抗肿瘤药物中的应用

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WO2015058126A1 (en) * 2013-10-18 2015-04-23 Syros Pharmaceuticals, Inc. Heteroaromatic compounds useful for the treatment of prolferative diseases
WO2015154039A2 (en) * 2014-04-04 2015-10-08 Syros Pharmaceuticals, Inc. Inhibitors of cyclin-dependent kinase 7 (cdk7)
WO2018013867A1 (en) * 2016-07-13 2018-01-18 Marineau Jason J Inhibitors of cyclin dependnt kinase 7 (cdk7)
WO2018098361A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinase 12 (cdk12) and uses thereof
CN109153675A (zh) * 2016-04-22 2019-01-04 达纳－法伯癌症研究所公司 细胞周期蛋白依赖性激酶9(cdk9)通过cdk9抑制剂与e3连接酶配体的缀合的降解及使用方法

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KR102668696B1 (ko) * 2012-01-12 2024-05-29 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
CA2927924A1 (en) * 2013-10-18 2015-04-23 Syros Pharmaceuticals, Inc. Heteroaromatic compounds useful for the treatment of proliferative diseases
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EP3445765A4 (en) * 2016-04-22 2019-09-18 Dana Farber Cancer Institute, Inc. DECREASE OF CYCLINE-DEPENDENT KINASE 4/6 (CDK4 / 6) BY CONJUGATION OF CDK4 / 6 INHIBITORS WITH E3-LIGASE LIGANDS AND METHODS OF USE
AU2019309909A1 (en) * 2018-07-23 2021-02-04 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use

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WO2015058126A1 (en) * 2013-10-18 2015-04-23 Syros Pharmaceuticals, Inc. Heteroaromatic compounds useful for the treatment of prolferative diseases
WO2015154039A2 (en) * 2014-04-04 2015-10-08 Syros Pharmaceuticals, Inc. Inhibitors of cyclin-dependent kinase 7 (cdk7)
CN109153675A (zh) * 2016-04-22 2019-01-04 达纳－法伯癌症研究所公司 细胞周期蛋白依赖性激酶9(cdk9)通过cdk9抑制剂与e3连接酶配体的缀合的降解及使用方法
WO2018013867A1 (en) * 2016-07-13 2018-01-18 Marineau Jason J Inhibitors of cyclin dependnt kinase 7 (cdk7)
WO2018098361A1 (en) * 2016-11-22 2018-05-31 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinase 12 (cdk12) and uses thereof

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Bivalent ligands for protein degradation in drug discovery;Marcel Scheepstra;Computational and Structural Biotechnology Journal;第17卷;160-176 *
Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC);Caroline M Robb;COMMUNICATION;第53卷(第54期);7577-7580 *
Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER);Jiantao Hu;Journal of Medicinal Chemistry;第62卷(第3期);1420-1442 *
Discovery of Wogonin-based PROTACs against CDK9 and Capable of Achieving Antitumor Activity;Jinlei Bian;Bio-Organic Chemistry;第81卷;373-381 *
Overview of CDK9 as a target in cancer research;Fatima Morales;CELL CYCLE;第15卷(第4期);519-527 *
pharmacological perturbation of CdK9 using selective CdK9 inhibition or degradation;Calla M Olson;nature CHeMICaL BIOLOGY;第14卷(第2期);163-170 *
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AU2020263390B2 (en) 2026-01-08
CA3132387A1 (en) 2020-10-29
US20220227734A1 (en) 2022-07-21
JP2022529700A (ja) 2022-06-23
EP3958861A1 (en) 2022-03-02
CN113993519A (zh) 2022-01-28
EP3958861A4 (en) 2023-05-03
WO2020219650A1 (en) 2020-10-29
AU2020263390A1 (en) 2021-10-07

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